Metabolome Analysis Revealed the Mechanism of Exogenous Glutathione to Alleviate Cadmium Stress in Maize (Zea mays L.) Seedlings

Cadmium (Cd) is one of the major heavy metal pollutants in the environment and imposes severe limitations on crop growth and production. Glutathione (GSH) plays an important role in plant Cd tolerance which is able to scavenge stresses-induced reactive oxygen species (ROS) and is involved in the biosynthesis of phytochelatins (PCs). Our previous study revealed that Cd stress affects maize growth, and the GSH treatment could relieve Cd stress in maize seedlings. In this study, we attempted to characterize the metabolomics changes in maize leaves and roots under Cd stress and exogenous GSH conditions. We identified 145 and 133 metabolites in the leaves and roots, respectively. Cd stress decreased the tricarboxylic acid cycle (TCA cycle) metabolism and increased the amino acid contents in the leaves, while it decreased the amino acid contents, increased the TCA cycle metabolism, the sugar contents, and shikimic acid metabolism in the roots. On the other hand, exogenous GSH increased the GSH content, changed the production of metabolites related to antioxidant systems (such as ascorbic acid-related metabolites and flavonoid-related metabolites), and alleviated lipid peroxidation, thereby alleviating the toxic effect of Cd stress on maize. These findings support the idea that GSH alleviates Cd-induced stress in maize and may help to elucidate the mechanism governing Cd-induced stress and the GSH-driven alleviation effect.

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Effect of Huangqin Tang on Urine Metabolic Profile in Rats with Ulcerative Colitis Based on UPLC-Q-Exactive Orbitrap MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1874065 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Dunfang Wang ◽

Xuran Ma ◽

Shanshan Guo ◽

Yanli Wang ◽

Tao Li ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fatty Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Unsaturated Fatty Acids ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Q Exactive ◽

Therapeutic Mechanisms

As a classic prescription, Huangqin Tang (HQT) has been widely applied to treat ulcerative colitis (UC), although its pharmacological mechanisms are not clear. In this study, urine metabolomics was first analysed to explore the therapeutic mechanisms of HQT in UC rats induced by TNBS. We identified 28 potential biomarkers affected by HQT that might cause changes in urine metabolism in UC rats, mapped the network of metabolic pathways, and revealed how HQT affects metabolism of UC rats. The results showed that UC affects amino acid metabolism and biosynthesis of unsaturated fatty acids and impairs the tricarboxylic acid cycle (TCA cycle). UC induced inflammatory and gastrointestinal reactions by inhibiting the transport of fatty acids and disrupting amino acid metabolism. HQT plays key roles via regulating the level of biomarkers in the metabolism of amino acids, lipids, and so on, normalizing metabolic disorders. In addition, histopathology and other bioinformatics analysis further confirm that HQT altered UC rat physiology and pathology, ultimately affecting metabolic function of UC rats.

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Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

eLife ◽

10.7554/elife.72593 ◽

2021 ◽

Vol 10 ◽

Author(s):

Dylan Gerard Ryan ◽

Ming Yang ◽

Hiran A Prag ◽

Giovanny Rodriguez Blanco ◽

Efterpi Nikitopoulou ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Metabolic Response ◽

Tricarboxylic Acid Cycle ◽

Fumarate Hydratase ◽

Tca Cycle ◽

Comparative Approach ◽

Redox Biology ◽

The Tca Cycle

The Tricarboxylic Acid Cycle (TCA) cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in murine kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology and amino acid homeostasis.

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P207 Synergetic effect of amino acid and ketone metabolism underlies empagliflozin-mediated cardioprotection in the type 2 diabetic heart

European Heart Journal ◽

10.1093/ehjci/ehz872.077 ◽

2020 ◽

Vol 41 (Supplement_1) ◽

Author(s):

H Kouzu ◽

H Oshima ◽

T Miki ◽

A Kuno ◽

T Sato ◽

...

Keyword(s):

Amino Acid ◽

Survival Rate ◽

Molecular Mechanisms ◽

Synergetic Effect ◽

Tca Cycle ◽

Oxidative Capacity ◽

Metabolome Analysis ◽

Coa Transferase ◽

The Tca Cycle

Abstract Funding Acknowledgements Boehringer Ingelheim Background Although emerging evidence has indicated that sodium glucose cotransporter 2 (SGLT2) inhibitors restore impaired cardiac energetics in type 2 diabetes mellitus (T2DM), the underlying molecular mechanisms have yet to be established. Augmented utilization of ketone is one proposed hypothesis, but depletion of succinyl-CoA triggered by the conversion of ketone back to acetyl-CoA by SCOT (succinyl-CoA:3-oxoacid CoA transferase) may hamper oxidative capacity of the tricarboxylic acid (TCA) cycle, which also requires succinyl-CoA. The recent finding that empagliflozin augments systemic amino acid metabolism in patients with T2DM led us to hypothesize that the anaplerotic effect of amino acid on the TCA cycle complements ketone oxidation. Methods and Results Myocardial infarction (MI) was induced in T2DM rats (OLETF) and control rats (LETO). Survival rate at 48 hours after MI was significantly lower in OLETF than in LETO (40% vs 84%), and empagliflozin treatment (10 mg/kg/day, 14 days) before MI improved the survival rate in OLETF to 70%. Metabolome analysis was performed using heart tissues from the non-infarct region 12 hours after MI. Using principal component analysis, data from 92 metabolites that were detected were compressed into 2 dimensions, and the first component (PC1) clearly separated empagliflozin-treated OLETF from non-treated LETO and OLETF. Analysis of factor loading of each metabolite for PC1 revealed that branched chain amino acids leucine, isoleucine and valine, the latter two of which can be oxidized to succynyl-CoA, and β-hydroxybutyrate were the top four metabolites that characterized empagliflozin treatment. Furthermore, in comparison to LETO, OLETF treated with empagliflozin showed 50% higher levels of glutamine and glutamate, both of which can replenish the TCA cycle at the level of α-ketoglutarate. In OLETF, empagliflozin significantly increased the TCA cycle intermediates citrate, cis-aconitate and malate by 74%, 119% and 59%, respectively. OLETF showed 86% higher lactate and 38% lower ATP than those in LETO, but levels of the metabolites were normalized by empagliflozin, suggesting improved glucose oxidation. Conclusions The present analyses showed that amino acid and ketone metabolism are metabolic pathways that are most affected by empagliflozin. Coordination of these "starvation-induced pathways" may underlie the favorable metabolic effect of empagliflozin in T2DM hearts.

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Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

10.1101/2021.07.27.453996 ◽

2021 ◽

Author(s):

Dylan Gerard Ryan ◽

Ming Yang ◽

Hiran A Prag ◽

Giovanny Rodriguez Blanco ◽

Efterpi Nikitopoulou ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Metabolic Response ◽

Tricarboxylic Acid Cycle ◽

Fumarate Hydratase ◽

Tca Cycle ◽

Comparative Approach ◽

Redox Biology ◽

The Tca Cycle

The Tricarboxylic Acid Cycle (TCA) cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology and amino acid homeostasis.

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Tricarboxylic Acid Cycle-Dependent Attenuation of Staphylococcus aureus In Vivo Virulence by Selective Inhibition of Amino Acid Transport

Infection and Immunity ◽

10.1128/iai.00195-09 ◽

2009 ◽

Vol 77 (10) ◽

pp. 4256-4264 ◽

Cited By ~ 39

Author(s):

Yefei Zhu ◽

Yan Q. Xiong ◽

Marat R. Sadykov ◽

Paul D. Fey ◽

Mei G. Lei ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Amino Acid ◽

Tricarboxylic Acid Cycle ◽

Inverse Correlation ◽

Tca Cycle ◽

Selective Inhibition ◽

Tricarboxylic Acid ◽

Glutamine Transporter ◽

Cycle Dependent

ABSTRACT Staphylococci are the leading causes of endovascular infections worldwide. Commonly, these infections involve the formation of biofilms on the surface of biomaterials. Biofilms are a complex aggregation of bacteria commonly encapsulated by an adhesive exopolysaccharide matrix. In staphylococci, this exopolysaccharide matrix is composed of polysaccharide intercellular adhesin (PIA). PIA is synthesized when the tricarboxylic acid (TCA) cycle is repressed. The inverse correlation between PIA synthesis and TCA cycle activity led us to hypothesize that increasing TCA cycle activity would decrease PIA synthesis and biofilm formation and reduce virulence in a rabbit catheter-induced model of biofilm infection. TCA cycle activity can be induced by preventing staphylococci from exogenously acquiring a TCA cycle-derived amino acid necessary for growth. To determine if TCA cycle induction would decrease PIA synthesis in Staphylococcus aureus, the glutamine permease gene (glnP) was inactivated and TCA cycle activity, PIA accumulation, biofilm forming ability, and virulence in an experimental catheter-induced endovascular biofilm (endocarditis) model were determined. Inactivation of this major glutamine transporter increased TCA cycle activity, transiently decreased PIA synthesis, and significantly reduced in vivo virulence in the endocarditis model in terms of achievable bacterial densities in biofilm-associated cardiac vegetations, kidneys, and spleen. These data confirm the close linkage of TCA cycle activity and virulence factor production and establish that this metabolic linkage can be manipulated to alter infectious outcomes.

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Involvement of enzymes of amino acid metabolism and tricarboxylic acid cycle in bovine oocyte maturation in vitro

Reproduction ◽

10.1530/rep.0.1260753 ◽

2003 ◽

pp. 753-763 ◽

Cited By ~ 40

Author(s):

P Cetica ◽

L Pintos ◽

G Dalvit ◽

M Beconi

Keyword(s):

Amino Acid ◽

Isocitrate Dehydrogenase ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Cumulus Cells ◽

Tricarboxylic Acid ◽

Maturation In Vitro

Few studies demonstrate at a biochemical level the metabolic profile of both cumulus cells and the oocyte during maturation. The aim of the present study was to investigate the differential participation of enzymatic activity in cumulus cells and in the oocyte during in vitro maturation (IVM) by studying the activity of enzymes involved in the control of amino acid metabolism, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and the tricarboxylic acid (TCA) cycle, isocitrate dehydrogenase (IDH) and malate dehydrogenase (MDH). No NAD-dependent isocitrate dehydrogenase (NAD-IDH) activity was recorded in cumulus-oocyte complexes (COCs). ALT, AST, NADP-dependent isocitrate dehydrogenase (NADP-IDH) and MDH enzymatic units remained constant in cumulus cells and oocytes during IVM. Specific activities increased in oocytes and decreased in cumulus cells as a result of IVM (P<0.05). Similar activity of both transaminases was detected in cumulus cells, unlike in the oocyte, in which activity of AST was 4.4 times greater than that of ALT (P<0.05). High NADP-IDH and MDH activity was detected in the oocyte. Addition of alanine, aspartate, isocitrate + NADP, oxaloacetate or malate + NAD to maturation media increased the percentage of denuded oocytes reaching maturation (P<0.05), in contrast to COCs in which differences were not observed by addition of these substrates and co-enzymes. The activity of studied enzymes and the use of oxidative substrates denotes a major participation of transaminations and the TCA cycle in the process of gamete maturation. The oocyte thus seems versatile in the use of several oxidative substrates depending on the redox state.

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Microarray and metabolome analysis of hepatic response to fasting and subsequent refeeding in zebrafish (Danio rerio)

BMC Genomics ◽

10.1186/s12864-019-6309-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Jirong Jia ◽

Jingkai Qin ◽

Xi Yuan ◽

Zongzhen Liao ◽

Jinfeng Huang ◽

...

Keyword(s):

Compensatory Growth ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Metabolome Analysis ◽

Cellular Mechanisms ◽

Metabolic Adaptations ◽

Dna Replication And Repair ◽

The Impact ◽

Metabolome Data ◽

Zebrafish Liver

Abstract Background Compensatory growth refers to the phenomenon in which organisms grow faster after the improvement of an adverse environment and is thought to be an adaptive evolution to cope with the alleviation of the hostile environment. Many fish have the capacity for compensatory growth, but the underlying cellular mechanisms remain unclear. In the present study, microarray and nontargeted metabolomics were performed to characterize the transcriptome and metabolome of zebrafish liver during compensatory growth. Results Zebrafish could regain the weight they lost during 3 weeks of fasting and reach a final weight similar to that of fish fed ad libitum when refed for 15 days. When refeeding for 3 days, the liver displayed hyperplasia accompanied with decreased triglyceride contents and increased glycogen contents. The microarray results showed that when food was resupplied for 3 days, the liver TCA cycle (Tricarboxylic acid cycle) and oxidative phosphorylation processes were upregulated, while DNA replication and repair, as well as proteasome assembly were also activated. Integration of transcriptome and metabolome data highlighted transcriptionally driven alterations in metabolism during compensatory growth, such as altered glycolysis and lipid metabolism activities. The metabolome data also implied the participation of amino acid metabolism during compensatory growth in zebrafish liver. Conclusion Our study provides a global resource for metabolic adaptations and their transcriptional regulation during refeeding in zebrafish liver. This study represents a first step towards understanding of the impact of metabolism on compensatory growth and will potentially aid in understanding the molecular mechanism associated with compensatory growth.

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Metabolomics Analysis in Different Development Stages on SP0 Generation of Rice Seeds After Spaceflight

Frontiers in Plant Science ◽

10.3389/fpls.2021.700267 ◽

2021 ◽

Vol 12 ◽

Author(s):

Deyong Zeng ◽

Jie Cui ◽

YiShu Yin ◽

Yi Xiong ◽

Mengyao Liu ◽

...

Keyword(s):

Amino Acid ◽

Stress Response ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Cycle Rate ◽

Development Stages ◽

The Tca Cycle ◽

Rice Seeds

Spaceflight is a special abiotic stress condition. In recent years, it has been confirmed that the spaceflight caused the stress response of rice seeds, and the protein level, transcription level, and methylation level will change during the planting process after returning to the ground. However, the changes at the metabolome level are not very clear. In this study, two kinds of rice seeds, Dongnong423 (DN3) and Dongnong416 (DN6), were carried on the ShiJian-10 retractable satellite (SJ-10) for 12.5 days in orbit, returned to the ground and planted in the field until the three-leaf (TLP) and tillering stage (TS). The results of antioxidant enzyme activity, soluble sugar, and electron leakage rate revealed that the spaceflight caused the stress response of rice. The TLP and TS of DN3 identified 110 and 57 different metabolites, respectively, while the TLP and TS of DN6 identified 104 and 74 different metabolites, respectively. These metabolites included amino acids, sugars, fatty acids, organic acids and secondary metabolites. We used qRT-PCR technology to explore the changes of enzyme genes in the tricarboxylic acid cycle (TCA) and amino acid metabolism pathway. Combined with the results of metabolomics, we determined that during the TLP, the TCA cycle rate of DN3 was inhibited and amino acid metabolism was activated, while the TCA cycle rate of DN6 was activated and amino acid metabolism was inhibited. In TS, the TCA cycle rate of DN3 was inhibited, and amino acid metabolism was not significantly changed, while the TCA cycle rate of DN6 was activated and amino acid metabolism was inhibited. These results suggested that the response mechanisms of the two different rice strains to spaceflight stress are different, and these differences may be reflected in energy consumption and compound biosynthesis of rice in different growth and development stages. This study provided new insights for further exploring the effects of spaceflight.

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